Staphylococcus aureus remains the main cause of hospital-acquired infections worldwide, exacerbated by the ongoing rise of resistance. Antibiotic combination therapy has been recommended for serious patients infected with multidrug-resistant organisms. Ceftaroline (CPT) exhibited bactericidal effects on S. aureus, whereas gentamicin (GEN) showcased broad-spectrum efficacy against various pathogens. This study aimed to investigate the synergistic effects of combining CPT and GEN and evaluate their potential in inhibiting the development of antibiotic resistance in S. aureus ATCC 29213. The minimum inhibitor concentrations (MICs) of each antibiotic were assessed using the serial dilution method. The synergistic efficacy of this combination was evaluated by the checkerboard titration method based on the fraction inhibitory concentration index (FICI) values. The resistance development of S. aureus to each antibiotic and their combination were also investigated over a 14-day exposure period. Moreover, the antibiotic susceptibility profile of the obtained strains after 14 days of exposure was determined using the Kirby-Bauer method’s disk diffusion. The result showed that the CPT-GEN combination displayed an additive effect, suggesting their compatibility in treatment without compromising efficacy. Following the 14-day exposure, S. aureus resisted both monotherapy and combination therapy. CPT alone or with sub-MIC GEN (1 μg/mL) prevented the rise of MIC value, while GEN alone or with sub-MIC CPT (0.5 μg/mL) did not prevent resistance. Furthermore, the antibiotic-exposed strains only developed resistance to GEN and penicillins (oxacillin) but not to other antibiotics. Overall, CPT and GEN did not express synergistic effects and combining CPT with low-dose GEN inhibited the resistance development in S. aureus ATCC 29213.